Biomedical subjects

B Claustrat

Publications and source records attributed to B Claustrat.

At least 91 records · Page 5Linked to original sources

PubMed1988

The TSH secretion in the human pituitary adenomas.

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.

Adenoma↗

PubMed1988

Plasma, cerebrospinal fluid, and brain distribution of 14C-melatonin in rat: a biochemical and autoradiographic study.

The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutes later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites.

Animals↗

PubMed1988

Plasma alpha-subunit levels during the treatment of pituitary adenomas with the somatostatin analog (SMS 201-995).

The effect os SMS 201-995 (Sandostatin), a long-acting somatostatin analog, on different types of pituitary adenomas including alpha-subunit elevation is illustrated in this report. Treatment induced a fall in hCG levels in a woman with a pituitary adenoma producing only alpha-subunit. In 3 acromegalic patients, there was only a partial drop in GH and alpha-hCG. The same effect was observed in a woman with menopausal FSH and LH levels. SMS reduced plasma TSH and alpha-hCG in a case of thyrotropic adenoma. Two patients exhibiting FSH- and alpha-hCG-secreting adenomas did not respond to acute administration of SMS 201-995. More patients have to be treated before a definitive statement can be made on the usefulness of somatostatin analogs in the management of different types of pituitary adenomas.

Adenoma↗

PubMed1988

Gonadotropin-releasing hormone agonists are unsuccessful in reducing tumoral gonadotropin secretion in two patients with gonadotropin-secreting pituitary adenomas.

Whether GnRH agonist treatment leads to reduced gonadotropin secretion and tumor volume in patients with gonadotropin-secreting pituitary adenomas is controversial. We studied the effect of GnRH analog treatment in two such patients, one with a recurrent FSH- and LH-secreting pituitary adenoma (patient 1) and one with a recurrent FSH- and alpha-subunit-secreting pituitary adenoma (patient 2). Patient 1 was treated with 200 micrograms Buserelin daily for 65 days, and patient 2 received three injections of 3 mg [D-Trp6]-LHRH formulated in microcapsules at 21-day intervals. In both patients, plasma FSH, LH (RIA), and alpha-subunit concentrations increased initially and remained above the pretreatment values throughout the treatment period. Plasma LH, measured by immunoradiometric assay, remained well above the detection limit. Plasma bioactive LH and testosterone became undetectable in patient 2, but did not change in patient 1. In neither patient did pituitary tumor size (determined by computed tomographic scan) change during treatment. We conclude that 1) the overall effect of GnRH analogs in patients with gonadotroph cell adenomas is stimulation of gonadotropin release by the tumor, although LH release varies according to how plasma LH is measured, possibly related to the origin of the hormone (normal or tumor gonadotroph cells), and 2) GnRH analog treatment does not reduce tumor size.

Adenoma↗

PubMed1988

Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans.

An oral preparation of melatonin was administered daily at 22.00 h to 6 healthy volunteers during summer on 4 consecutive days (days 1-4). The daily dose was 8 mg of melatonin as a single. Three 24-h melatonin, cortisol and prolactin profiles were determined in plasma by radioimmunological methods: 1) before treatment (day 0); 2) the first day after the 4-day treatment had been stopped (day 5), 3) the third day after withdrawal of this treatment (day 7). For the melatonin rhythm, an advanced phase was observed at day 7 vs day 0, whereas the amplitude and the mesor were not modified, whatever the day. For the prolactin profile, a significant increase as compared with the control day (day 0) was detected only at day 7 between 19.00 and 21.00 h. No modification was recorded for the plasma cortisol secretion. These results suggest that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion. This effect must be investigated over several days after the treatment has ended.

Adult↗

PubMed1987

[Dexamethasone suppression test in psychiatric pathology].

The dexamethasone suppression test (DST) has been used in psychiatric pathology for about 10 years. Carroll et al. consider this test to be specific of endogenous depression. According to these, and many other authors, approximately 55% of patients with endogenous depression show a positive response to the test, whereas a positive response is observed in only 4% of normal subjects or patients with psychiatric disorders other than major depressive disorders. The DST was performed in 162 psychiatric inpatients (5 with organic disease, 28 with schizophrenic disorders, 17 with major affective disorders, 5 with obsessive compulsive disorders, 103 with dysthymic disorders and 4 unclassified). Dexamethasone (1 mg) was administered orally at 11 p.m., and plasma cortisol concentration was measured the following day at 16 p.m. Response to the test was positive in 53% of patients with major affective disorders, 25% of those with schizophrenic disorders, 60% with obsessive compulsive disorders and 18% with dysthymic disorders. There was no statistical difference in the results according to age, sex ratio, family history of depression or duration of the disorders. Only two variables were close to the P less than 0.05 level of statistical significance: severity of the disorders and early morning awakening. DST sensitivity, therefore, would appear to be about 50% in major affective disorders, but this test is not specific as it may also be positive in other psychiatric disorders. A positive dexamethasone suppression test may be regarded as a sign of severity of psychiatric disorders.

Depressive Disorder↗

PubMed1987

Detection and enzymatic deglycosylation of a glycosylated variant of prolactin in human plasma.

Immunoperoxidase electrophoresis was applied to the plasma of a patient showing a high level of prolactin (PRL) secreted by a pituitary adenoma. Two PRL monomers were detected with an anti-hPRL antiserum: a major 22 kDa form and a minor 25 kDa form. Concanavalin A-Sepharose 4B chromatography revealed that the 25 kDa form was a glycosylated variant of PRL. Incubation of this variant with endoglycosidase F led to its transformation into the 22 kDa form.

Adenoma↗

PubMed1987

Effects on the patterns of melatonin and cortisol in cluster headache of a single administration of lithium at 7.00 p.m. daily over one week: a preliminary report.

Cluster headache represents a primary headache disorder. The major characteristics of cluster headache are the seasonal frequency and the occurrence of symptoms during night time. A significant decrease in nocturnal melatonin levels and an advanced phase associated with a shift in cortisol acrophase has been described. The effect of lithium on nocturnal melatonin and cortisol secretion was examined in the present study. Preliminary results indicate that Lithium delaises rhythms in cluster head-ache.

Adult↗

PubMed1987

Urinary melatonin, LH, oestradiol, progesterone excretion during the menstrual cycle or in women taking oral contraceptives.

Nocturnal urinary excretion of melatonin, LH, progesterone and oestradiol was measured by radioimmunoassay in nine normal women during a complete cycle. In addition, these hormonal excretions were studied in two women taking an oral contraceptive. A high within-subject coefficient of variation was observed for melatonin excretion in the two groups. In the nine normal cycling women, melatonin excretion was not decreased at the time of ovulation, but was significantly increased during the luteal phase compared with that of the follicular phase (P less than 0.01). These data are consistent with a positive relationship between melatonin and progesterone during the luteal phase. In the two women under an oral contraceptive, melatonin excretion was found within the same range as for the other nine. The results are discussed in terms of pineal investigation in human.

Adult↗

PubMed1986

Decreased nocturnal plasma melatonin peak in patients with a functional alteration of the retina in relation with uveitis.

A functional alteration of the retina is present in patients suffering from uveitis. Because of the relation between the pineal gland and the retina we documented possible modifications of melatonin secretion in patients with uveitis. Plasma melatonin was assayed in 19 patients and 16 age-matched controls. Blood samples were drawn at the known high and low points of the circadian rhythm of the hormone, i.e. 02.00 and 11.00 h, respectively. We found that the nocturnal peak of plasma melatonin was greatly decreased (45%) in patients with uveitis. These data cannot be related to the impairment of retinal melatonin synthesis alone. The possibility exists that the decline of the nocturnal peak of melatonin we have reported is due to a pineal inflammation in patients with uveitis, as observed in the experimental autoimmune uveitis induced in rats by retinal S-antigen.

Adolescent↗

PubMed1986

Synthetic human growth hormone releasing factor (h-GRF-I-44-NH2) dose response effect on growth hormone and prolactin secretion in healthy adult men.

The dose-effect relationship of an i.v. bolus of synthetic h-GRF-44 on growth-hormone and prolactin secretion has been studied. Seven healthy adult volunteers received in a random order h-GRF-44 2.5, 5, 10, 20, 40 and 80 micrograms and a placebo. Plasma growth hormone (GH) was determined between 30 min before and 240 min after injection, the area under the curve (AUC) and the peak GH level being used to assess the response. For both parameters a dose-effect relationship was observed. Doses as low as 2.5 micrograms were capable of eliciting a rise in GH plasma levels in few patients. Above 40 micrograms the dose-effect curves tended to plateau, although the decrease in the slope of the dose-effect curve at the peak was more marked. Intersubject variability was large, so precise determination of the minimal effective dose as well as the lowest dose giving a maximal effect was not possible. The available evidence suggests that the i.v. dose of synthetic h-GRF-44 (SR 95228) which is likely to promote GH release into the blood stream in most healthy adults is within the range 40-100 micrograms. In these healthy adults unwanted effects were infrequent with these low doses. Unlike previous experience with higher doses of another synthetic h-GRF-44, prolactin secretion in this study was not affected.

Adult↗

PubMed1986

Clinical studies with human growth hormone releasing factor in normal adults and patients.

The recent availability of human growth hormone releasing factor (hGRF) encouraged thorough investigations of human growth hormone secretion. Moreover it is now possible to put forward a therapeutic application for this hormone. Herein, we report the dose-effect relationship obtained between hGRF and GH response in normal young men submitted to IV administration of doses ranging from 2.5 to 600 micrograms per subject, in three protocols. In some subjects the 2.5 micrograms dose elicited GH secretion as compared with placebo. A highly significant dose-effect was observed (based on GH-AUC and GH-peak) for doses ranging from 5 to 80 micrograms. Responses were identical above 80 micrograms. We conclude that the optimal dose required to elicit maximum GH release with minimal unwanted effects is 80 micrograms in adults. These are related to the dose and observed for doses up to 80-150 micrograms. Subcutaneous administration also induced GH-release, with relationship to the doses used (100, 300 and 600 micrograms per subject). The mean response to the highest dose (600 micrograms) was comparable in timing and magnitude to that obtained with a 100 microgram intravenous dose. Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay and a high correlation was obtained between bioassay and radioimmunoassay. GH was present in blood after hGRF under 3 molecular forms corresponding to little, big and big-big GH with percentages of 50, 30 and 20, respectively. An early and slight increase in prolactin was found to be related to the hGRF doses above 80 micrograms. No change was observed for doses less than 80 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1986

A once-repeated study of nocturnal plasma melatonin patterns and sleep recordings in six normal young men.

The concentration of melatonin was determined, using a sensitive and reliable radioimmunoassay, in plasma samples obtained at 20 min intervals during a 12 hr period (from 20.00 to 8.00) from six normal men. Polygraphic sleep recording was simultaneously performed. Each subject was studied twice at a 1 week interval. For each session, the plasma melatonin profile showed an episodic secretion: a mean frequency of 4.5 peaks and 4.0 troughs per night in the first study and a mean frequency of 4.0 peaks and 3.5 troughs in the second study. The two nocturnal melatonin profiles obtained from each subject were very similar. However, considerable interindividual variation was found (areas under the curve [AUC] from 15.3 to 125 pg X hr/ml). No relationship could be obtained between AUC and body weight. Apparent melatonin half-life calculated from the semilogarithmic plots of the melatonin pattern was 57 +/- 34 min. Chi-square testing revealed that the nocturnal pattern of melatonin levels was not related to sleep stages. Our data do not favor a direct relationship between melatonin secretion and the sleep-waking cycle in humans.

Adult↗

PubMed1986

Diurnal variations of plasma melatonin concentrations in pregnant or pseudopregnant mink (Mustela vison) maintained under different photoperiods.

Removal of the superior cervical ganglia suppresses the inhibitory role of short days in prolactin secretion and luteal activity in pregnant or pseudopregnant mink. Alternatively, timed injections of melatonin replicate the inhibitory role of short days in females maintained under long days. To understand if the diurnal variation of melatonin secretion is part of the mechanism by which the mink measure day length, diurnal variations in plasma melatonin concentrations have been measured in intact and ganglionectomized females maintained under long or short days after mating. Melatonin was measured by radioimmunoassay according to Brun et al. [Adv. Biosci. 53:41-45]. In intact females, plasma concentrations ranged from nondetectable levels to 40 pg/ml during the day, increased shortly after the onset of the dark phase, and reached peak values during the middle of the night. The duration of the elevated levels was roughly proportional to the length of the night. No diurnal variations could be detected in ganglionectomized females; melatonin levels never exceeded the day values observed in intact females.

Animals↗

PubMed1986

Investigation of human growth hormone releasing factor in adults.

A dose-effect relationship between human growth hormone (GH) releasing factor (hGRF) and GH response was demonstrated for doses ranging from 5 micrograms per subject (minimal active dose) to 40-80 micrograms per subject (minimal dose for maximal effect). Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay. Unwanted effects were observed for doses equal to or larger than 150 micrograms. Pharmacokinetic parameters were calculated from the immunoreactive GRF plasma concentrations obtained after intravenous injections of various doses. The half-lives were 6.8 +/- 0.4 min and 43.2 +/- 3 min for distribution and elimination phases, respectively. Subcutaneous administration of hGRF was shown to be effective for promoting GH release, with doses higher than those required by intravenous administration. Intermittent intravenous injection of hGRF, at 3-hour intervals, resulted in a decrease in the magnitude of GH response in normal subjects.

Acromegaly↗

PubMed1986

Pituitary stimulation by combined administration of four hypothalamic releasing hormones in normal men and patients.

Ten normal young men (22-28 yr of age), within 10% of their ideal body weight, were given the four releasing hormones (TRH, 200 micrograms; GnRH, 100 micrograms; ovine corticotropin-releasing hormone, 50 micrograms; GH-releasing hormone, 80 micrograms) iv on separate days and then in combination on the same day. Plasma TSH, PRL, FSH, LH, cortisol, ACTH, and GH were measured by RIA in samples collected from 20 min before to 120 min after injection. There were no significant differences in responses to the separate and combined tests for FSH, LH, cortisol, ACTH, and GH. The plasma TSH (0.001 less than P less than 0.01) and PRL (P less than 0.001) responses were significantly higher after the combined test. The tolerance was identical to that of TRH alone. In eight patients studied after pituitary surgery, combined administration provided results comparable to those obtained after separate administration of TRH, GnRH, and insulin.

Adenoma↗

PubMed1986

The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors.

Twenty-six out of 400 surgically removed pituitary tumors were identified as gonadotropic adenomas (frequency 6.25%). Morphologic, immunocytochemical, and hormonal characteristics of the gonadotropic adenoma are described. The following morphologic characteristics may suggest the diagnosis: arrangement in cords of cells showing signs of cellular activity, secretory granules, which vary in electron density, form, and size (mean diameter 150 nm) and which are numerous in the extensions near the capillaries, and a rough endoplasmic reticulum arranged in short cisternae. However, owing to the morphofunctional variations from one adenoma to another, we consider that only immunoreactivity with gonadotropin antisera proves the diagnosis. Because the material used to generate the gonadotropin antisera was purified but not pure, for precise characterization of the immunoreactivity, absorption tests with various antigens have to be performed. FSH-LH adenomas (n = 14), FSH adenomas (n = 7), and alpha-subunit adenomas (n = 5) but no LH adenomas were identified in our series. No evident morphologic difference related to the type of immunoreactivity and to the sex was found. Almost all the tumors were large with visual signs caused by suprasellar extension. A recurrence following adenomectomy was noted with a frequency of 12%. The diagnosis of gonadotropic adenoma was considered preoperatively in six out of 26 patients only, on the basis of increased serum gonadotropin levels. Correlations between hormonal levels and pathologic data were established in 17 patients. Seven tumors were associated with high serum gonadotropin levels (FSH and LH: three patients and FSH alone: four patients). In ten cases, the serum gonadotropin levels were normal but serum alpha-subunit assay had not been performed. For the pathologist systematically testing the adenomas with many antisera, gonadotropic adenomas are not as rare as for the clinician. Immunocytochemical studies with gonadotropin antisera and serum gonadotropic determination must be performed in all tumors, especially in those pituitary adenomas that appear nonfunctional.

Adenoma↗

PubMed1986

The human thyrotropic adenoma: pathologic diagnosis in five cases and critical review of the literature.

Five out of 400 surgically removed pituitary tumors (frequency: 1.2%) were identified as thyrotropic adenomas according to the following criteria: identification of tumoral thyrotropic cells by immunocytochemistry and ultrastructural study; elevated serum TSH levels with decrease after surgery; and elevated concentration of TSH in the tumor. Four patients presented with hyperthyroidism and one with euthyroidism. From these five cases and 11 similar observations extracted from a critical review of literature, the morphologic, immunocytochemical, and hormonal characteristics of thyrotropic adenoma are described. Thyrotropic adenomas are more often large tumors but may also be microadenomas. The diagnosis is asserted by immunoreactivity with anti-TSH antisera. The TSH positive tumor cells are numerous. In some tumors, rare cells of other types are also found (PRL, GH, FSH, or ACTH cells). Some morphologic characteristics strongly suggest the diagnosis. The cells are often large with thin processes. They show argyrophil granulations in a slightly basophil cytoplasm and signs of secretory activity. Their secretory granules are round and small without striking variations in size, shape, and electron density. Elevated concentration of TSH in the tumor confirms the diagnosis. The presence of high serum TSH levels and a molar ratio of alpha hTSH to the whole TSH molecule greater than one are other good criteria. Decrease of TSH after surgery may not be observed in invasive tumors. TSH adenoma is most often associated with hyperthyroidism but it can also be associated with hypothyroidism or euthyroidism.

Adenoma↗